Sparks - Cereno Scientific

Cereno Scientific has announced first site activation in its global Phase IIb EPIMODE study of CS1 in pulmonary arterial hypertension (PAH), marking the transition from trial preparation to active patient recruitment. We view this as a meaningful de-risking event for CS1, with additional site activations expected to progressively expand recruitment capacity. The study will enrol 126 patients across 68 sites in 12 countries (in North America, Europe and South America) and evaluate CS1 as an add-on to stable standard-of-care therapy versus placebo. CS1 is an oral, once-daily HDAC inhibitor that acts through epigenetic modulation, targeting underlying PAH disease biology, including vascular remodelling, fibrosis and inflammation, rather than solely addressing symptoms and haemodynamics.

Importantly, the total trial duration will be 56 weeks with the study employing a differentiated two-stage design: patients initially receive one of two CS1 doses or placebo for nine months (36 weeks), followed by re-randomisation, whereby CS1-treated patients either continue therapy or switch to placebo, while placebo patients cross over to active treatment for the remaining trial duration. This ensures that all trial participants receive active treatment at some point while also allowing Cereno to assess the evolution and durability of treatment effects following continued therapy or treatment switching, potentially providing additional evidence for CS1’s proposed disease-modifying effects. The primary endpoint will be change in pulmonary vascular resistance at nine months, providing an objective haemodynamic efficacy measure. Additional assessments include right-heart function, functional capacity, risk evaluation, biomarkers, clinical worsening, patient-reported outcomes and pharmacokinetics. Top-line data are expected in Q428 (subject to recruitment timelines), providing the next major clinical value inflection point for CS1.